Drug repurposing is a term applied to finding a new therapeutic and pharmacological indication for an existing drug molecule with a known indication. Repurposing existing drugs to treat both rare and widespread ailments is more and more compelling due to the use of less risky compounds, which may result in lower entire development costs and quicker development timelines. This is due to the high attrition rates, high cost, and slow new drug discovery and development pace. The introduction of computational techniques and their advancements in drug design, discovery, and development has provided a platform for scientists to kick-start drug repurposing with ease. Computational approaches have provided rationality in drug repurposing, reducing the chances of failure in drug repurposing attempts. In this chapter, we present techniques for drug repurposing that are both conventional and computational, talk about the difficulties faced by scientists who attempt drug repurposing, and suggest creative solutions to these difficulties to help drug repurposing reach its full potential.

The continuous destruction of normal insulin-producing pancreatic beta-cells is a contributing factor in all common forms of diabetes, due to insufficient production of insulin, especially in type 1 diabetes. There are attempts at beta-cells transplantation, but the cost and availability of donors pose a great challenge to the process. Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase A (DYRK1A) plays a crucial role in beta-cells destruction. Our research targets to identify plants that can be utilized as a possible alternative approach to beta-cell replacement through a pharmacologically induced regeneration of new beta-cells in-silico. The 3D structure DYRK1A and 6511 phytochemicals were obtained from the Protein Data Bank and the African Natural Products Database respectively. They were duly prepared for molecular docking simulations (MDS). MDS was implemented, after validation of docking protocols, in AutoDock-Vina®, with virtual screening scripts. Phytocompounds with good binding affinities for DYRK1A were selected as frontrunners. The compounds were screened for toxicity, Lipinski’s rule confirmation with Data Warrior software followed by kinase inhibitory bioactivity prediction with the Molinspiration Chemoinformatics web tool. Twelve phytocompounds were found to be predictably highly active in-silico against DYRK1A with good drug-like property based on Lipinski’s rule, non-mutagenic, non-tumorigenic, no reproductive effect, and non-irritant, with high predicted bioactivity. In-silico active phytocompounds against DYRK1A with their plant sources and physicochemical parameters were identified. Further studies will be carried out in-vitro and in-vivo to validate the results of this study using plants containing the identified phytocompounds.

Lassa fever (LF), a viral hemorrhagic fever disease with a case fatality rate that can be over 20% among hospitalized LF patients, is endemic to many West African countries. Currently, no vaccines or therapies are specifically licensed to prevent or treat LF, hence the significance of developing therapeutics against the mammarenavirus Lassa virus (LASV), the causative agent of LF. We used in silico docking approaches to investigate the binding affinities of 2015 existing drugs to LASV proteins known to play critical roles in the formation and activity of the virus ribonucleoprotein complex (vRNP) responsible for directing replication and transcription of the viral genome. Validation of docking protocols were achieved with reference inhibitors of the respective targets. Our in silico docking screen identified five drugs (dexamethasone, tadalafil, mefloquine, ergocalciferol, and flunarizine) with strong predicted binding affinity to LASV proteins involved in the formation of the vRNP. We used cell-based functional assays to evaluate the antiviral activity of the five selected drugs. We found that flunarizine, a calcium-entry blocker, inhibited the vRNP activity of LASV and LCMV and virus surface glycoprotein fusion activity required for mammarenavirus cell entry. Consistently with these findings, flunarizine significantly reduced peak titers of LCMV in a multi-step growth kinetics assay in human A549 cells. Flunarizine is being used in several countries worldwide to treat vertigo and migraine, supporting the interest in exploring its repurposing as a candidate drug to treat LASV infections.

Picralima nitida the only species in the genus Picralima belongs to the Apocyanaceae family. It is widely known for its medicinal purposes. The aim of the study was to investigate pharmacognostic parameters of the leaf and evaluate the hepatoprotective activity against carbon tetrachloride induced hepatotoxicity using Swiss Albino mice. The physicochemical evaluation indicated 11.75% moisture content, 8.50% total ash, 9.50% acid insoluble ash, 4.00% water soluble ash, 13.75% alcohol extractive value and 11.00% water extractive value. Macroscopic analysis on the fresh leaves revealed an odourless green plant with bitter taste. Microscopic examination indicated the presence of calcium oxalate crystals, starch grains, epidermal cells, xylem, parenchyma cells, paracytic stomata and palisade tissue. Chemomicroscopic evaluation indicated the presence of oxalate crystals, starch grains, lignified tissues, tannins, cellulose, protein and oil. The acute toxicity result revealed that P. nitida had no adverse effect in Swiss Albino mice. The ethyl acetate fraction had hepatoprotective ability on liver enzymes (alanine transaminase, aspartate aminotransferase, alkaline phosphatase) and can produce the same result as ascorbic acid (standard).

The prevalence of Diabetes mellitus (DM) is continuously rising worldwide. Among its types, type I is characterized by the destruction of beta cells triggered by various mechanisms, including the activation of Caspase 3. Studies have demonstrated the crucial role of Caspase 3 in initiating the apoptosis of beta cells in DM. Our research aims to identify possible phytocompounds inhibitors of Caspase 3 using computational approach. We obtained 3D structures of Caspase 3 and 6511 phytocompounds from the Protein Data Bank and the African Natural Products Database, respectively. The phytocompounds were assessed for druglikeness properties, topological polar surface area, and preliminary toxicity using DataWarrior. The phytocompounds were subjected to molecular docking simulation (MDS) at Caspase 3 active site using AutoDock-Vina. The frontrunner phytocompounds obtained from the MDS were subjected to protease inhibition prediction on Molinspiration. The pharmacokinetics of the phytocompounds were assessed on SwissADME. The in-depth computational toxicity profile of the phytocompounds was evaluated on the pkCSM web. The binding interactions of the phytocompounds with Caspase 3 were assessed with Discovery Studio Visualizer and Maestro. Seventeen phytocompounds were found to have no violation of Lipinski's rule and had no toxicity based on the preliminary assessment, have better binding affinity and protease inhibitory prediction scores than the references, have optimistic bioactivity radar prediction and similar amino acids interaction, in comparison with the references. Further studies, which include in-vitro and in-vivo studies, will be carried out to validate the results of this study.